Evidence map›Paper›PMID 41315209›Full record

ArticleNature communications2025

A niche-dependent redox rheostat regulates epithelial stem cell fate.

Xi Chen, Krishnan Raghunathan, Bin Bao, Elsy Ngwa, Andrew Kwong, Zhongyang Wu, Stephen Babcock, Clara Baek, George Ye, Anoohya Muppirala and 12 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Xi ChenDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.
Krishnan RaghunathanDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.
Bin BaoDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7610-3426
Elsy NgwaDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.
Andrew KwongDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.
Zhongyang WuDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.
Stephen BabcockDepartment of Pathology, Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA.
Clara BaekDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-0644-365X
George YeDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0003-1380-7121
Anoohya MuppiralaDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.
Qianni PengDepartment of Chemistry, Boston College, Chestnut Hill, MA, USA.
Michael RutlinDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.
Mantu BhaumikDepartment of Neurology, F.M. Kirby Neurobiology Center, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
Daping YangInstitute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Daniel KotlarzInstitute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Unmesh JadhavDepartment of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Meenakshi RaoDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8194-9204
Eranthie WeerapanaDepartment of Chemistry, Boston College, Chestnut Hill, MA, USA.ORCID 0000-0002-0835-8301
Xu ZhouDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-1692-6823
Jose Ordovas-MontanesDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5444-5601
Scott B SnapperDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0267-4247
Jay R ThiagarajahDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital; Harvard Medical School, Boston, MA, USA. jay.thiagarajah@childrens.harvard.edu.ORCID 0000-0002-1437-325X

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
COngenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepositoryRC2DK118640 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI James Richard Goldenring, Izumi Kaji · 2019 to 2026
$14.8M
Genetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI SCOTT Loren POMEROY, MUSTAFA SAHIN · 2021 to 2026
$9.4M
Identifying Immune and Epithelial Network Signatures in Very Early Onset Inflammatory Bowel DiseaseRC2DK122532 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI KLEIN, CHRISTOPH, MUISE, ALEIXO M · 2020 to 2024
$9.1M
Developing chemical-proteomic tools to investigate cysteine oxidationR35GM134964 · NIGMS · BOSTON COLLEGE · PI WEERAPANA, ERANTHIE · 2020 to 2024
$3.1M
Training in Developmental Biology, Stem Cells and RegenerationT32HD060549 · NICHD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Gage D Crump · 2011 to 2026
$2.5M
Decoding Hydrogen Peroxide Signaling at Cellular Membranes (Equipment Supplement)R35GM142683 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI THIAGARAJAH, JAY · 2021 to 2025
$2.3M
Understanding Immune-Stromal Interactions in Tissue Homeostasis and InflammationR35GM151000 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI XU ZHOU · 2023 to 2026
$1.8M
Redox-mediated regulation of pattern-recognition-receptor signaling in intestinal epithelial cellsR03DK125630 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI THIAGARAJAH, JAY · 2020 to 2021
$266k
NICHD NIH HHS P50 HD105351NICHD NIH HHS T32 HD060549NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R03 DK125630NIDDK NIH HHS RC2 DK118640NIDDK NIH HHS RC2 DK122532NIGMS NIH HHS R35 GM134964NIGMS NIH HHS R35 GM142683NIGMS NIH HHS R35 GM151000U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) P30DK034854U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R03DK125630U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) RC2DK122532U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM134964U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM151000U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) HD105351
6 · The paper itself

Abstract

Intestinal stem cells (ISCs) reside in regionally variable niches that provide diverse microenvironmental cues such as tissue oxygen status, and morphogen signaling. Integration of these cues with ISC metabolism and fate remains poorly understood. Here, we show that cellular redox balance orchestrates niche factors with metabolic state to govern cell fate decisions. We demonstrate that hypoxia and Wnt signaling synergistically restrict the reactive oxygen species generating enzyme NADPH oxidase 1 (NOX1) regionally to the crypt base in the distal colon. NOX1 enables maintenance of an oxidative cell state that licenses cell cycle entry, altering the balance of asymmetric ISC self-renewal and lineage commitment. Mechanistically, cell redox state directs a self-reinforcing circuit that connects hypoxia inducible factor 1α-dependent signaling with post-translational regulation of the metabolic enzyme isocitrate dehydrogenase 1. Our studies show redox balance acts as a cellular rheostat that is central and causative for metabolic control of the ISC cell-cycle.

Indexed as

Epithelial CellsStem Cell NicheStem CellsAnimalsCell CycleCell DifferentiationCell HypoxiaCell LineageColonHypoxia-Inducible Factor 1, alpha SubunitIntestinal MucosaIsocitrate DehydrogenaseMiceMice, Inbred C57BLNADPH Oxidase 1Oxidation-ReductionHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitIsocitrate DehydrogenaseNADPH Oxidase 1NOX1 protein, mouseReactive Oxygen Species

Identifiers

PMID41315209
PMCPMC12754055

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.